5613436 EXPERT CONSENSUS ON THE MANAGEMENT OF INFUSION-RELATED REACTIONS (IRRS) PRESENTING WITH PAIN IN PATIENTS RECEIVING CRIZANLIZUMAB
Authors: J. Kanter, K. Ataga, N. Bhasin, S. Guarino, A. Kutlar, S. Lanzkron, D. Manwani, P. McGann, S. Stowell, V. Tubman, I. Yermilov, C. Campos, M.S. Broder
Journal: HemaSphere (2023)

Background: Sickle cell disease (SCD) is characterized by the presence of sickle hemoglobin, hemolytic anemia, and multi-organ and vaso-occlusive complications that can significantly decrease quality of life.[1] Crizanlizumab, a monoclonal antibody, has been shown to reduce the rate of vaso-occlusive crises (VOCs) compared to placebo in patients ≥16 years with SCD.[2] However, there have been reports of patients experiencing severe pain and subsequent complications within 24 hours of crizanlizumab infusions, and these events are defined as infusion-related reactions (IRRs).[3] IRRs are rare, and most clinicians will have limited experience managing them. Aims: Develop clinical guidelines on the management of IRRs presenting with pain in SCD patients receiving crizanlizumab. Methods: We used the RAND/UCLA modified Delphi process. We convened a geographically diverse, experienced 10-member US physician panel (5 pediatric hematology, 4 adult hematology, 1 transfusion medicine) and reviewed evidence on the management of painful IRRs related to crizanlizumab in patients with SCD. We collaboratively developed a rating form made up of 204 hypothetical patient scenarios assessing how to monitor and treat IRRs that present with new or worsening pain. For each of these scenarios, which described different clinical characteristics (e.g., typical vs atypical SCD pain location, pain severity compared to patient’s typical SCD crisis), we asked how to monitor vital signs, when to change infusion speed or discontinue the infusion, which medications to add, which laboratory tests to order, and whether to escalate care (e.g., emergency department referral). Physicians completed ratings both before and after a virtual meeting in June 2022, during which areas of disagreement were discussed. Consensus was defined as being present when no more than two panelists gave a response that differed significantly from the other 8 panelists. Results: Expert recommendations on how to manage IRRs presenting with pain are delineated in Figure 1. When a patient presents with either chest pain of the same severity or pain in any location more severe than their typical SCD crisis, experts recommend continuous vital sign monitoring, stopping the infusion, ordering laboratory tests including a complete blood count, reticulocyte count, and electrolyte and liver function panels, and escalating post-infusion care. Pain should be treated per a patient’s individualized pain plan or other pain management guidelines. Experts do not recommend treating IRRs that present with pain with IV antihistamines or corticosteroids, which can worsen pain and provoke VOCs. Summary/Conclusion: These recommendations outline how to evaluate and manage IRRs presenting with pain in patients receiving crizanlizumab. A valid, reproducible method was used to develop these guidelines, based on expert consensus informed by current literature and clinical experience. Future research should validate this guidance using clinical data and identify patients at risk for these IRRs.References 1. Kavanagh et al. Pediatrics. 2015;136(4):e1016–25. 2. Ataga et al. N Engl J Med. 2017;376(5):429–39. 3. Safety of crizanlizumab [Internet]. [cited 2020 Oct 26]. Available from: https://www.crizanlizumab.info/